17 - Chapter 12 Other substances

01 - Caffeine

Caffeine

The Maudsley® Prescribing Guidelines in Psychiatry, Fifteenth Edition. David M. Taylor, Thomas R. E. Barnes and Allan H. Young. © 2025 David M. Taylor. Published 2025 by John Wiley & Sons Ltd. Chapter 12 Caffeine Caffeine is probably the most used psychoactive substance in the world. Mean daily consumption in the UK is 350–620mg.1 A quarter of the general population and half of  those with psychiatric illness regularly consume over 500mg caffeine per day.2 Consumption of caffeine should be routinely discussed with an individual to assess its effect on their symptoms and presentation.3 Both caffeine intake and caffeine withdrawal can have a marked effect on mental and physical health. Most caffeine intake is in the form of coffee and tea but increasingly in the form of energy drinks (Table 12.1). Caffeine is also a constituent of chocolate and hundreds of over-­the-­counter medicines where it is often included as a co-­analgesic. Other substances Table 12.1  Typical caffeine content of drinks. Drink Caffeine content Brewed coffee4 100mg/cup (around 100mg per espresso shot) Red Bull 80mg/can (other energy drinks may contain substantially more; volume of cans varies substantially) Instant coffee 60mg/cup Black tea 45mg/cup Soft drinks (sodas) 25–50mg/can Green tea 20–30mg/cup Decaffeinated coffee 3–16mg5

02 - General effects of caffeine

General effects of caffeine

03 - Psychotropic effects of caffeine

Psychotropic effects of caffeine

902 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 12 General effects of caffeine ■ ■Acute use can increase systolic and diastolic blood pressure (BP) by up to 10mmHg for up to 4 hours.3 Chronic moderate use probably has little effect on BP.9 ■ ■May enhance reinforcing effects of nicotine and possibly other drugs of misuse.10,11 ■ ■Caffeine has important psychotropic effects (Table  12.2), may worsen existing ­psychiatric illness and may interact with psychotropic drugs. ■ ■Caffeine is an antagonist at adenosine A1 and A2A receptors, thus stimulating ­dopamine pathways. Psychotropic effects of caffeine Withdrawal An established withdrawal syndrome exists; symptoms include headache, depressed mood, anxiety, fatigue, irritability, nausea, dysphoria and craving.12 Pharmacokinetics ■ ■Absorption: Rapid after oral administration, especially in liquid form. ■ ■Metabolism: ■ ■Half-­life of 2.5–4.5 hours. ■ ■Metabolised by CYP1A2, a hepatic cytochrome enzyme that exhibits genetic ­polymorphism. This may account for the large interindividual differences that are seen in the ability to tolerate caffeine.13 Note that CYP1A2 is induced by smoking and inhibited by a number of drugs such as fluvoxamine. ■ ■This metabolic pathway may become saturated at higher doses.14 ■ ■Interactions (Table 12.3): ■ ■Caffeine competitively inhibits CYP1A2. Chronic caffeine use may increase plasma levels of drugs metabolised by CYP1A2. Plasma levels of some drugs may be reduced if caffeine is withdrawn. Table 12.2  Dose and psychotropic effects of caffeine. Dose Psychotropic effect Generally Central nervous system stimulation Increase catecholamine release, particularly dopamine6 Low to moderate dose2,7 Elation Impulsivity Peacefulness Large doses >600mg/day8 (sensitive [non-­tolerant] individuals may experience effects at lower doses; tolerance develops in long-­term users) Anxiety Insomnia Psychomotor agitation Excitement Rambling speech Delirium Psychosis

04 - Caffeine intoxication

Caffeine intoxication

Other substances CHAPTER 12 ■ ■The potential effects of caffeine on the metabolism of other drugs, as well as the potential to induce a caffeine withdrawal syndrome, should always be considered before substituting caffeine-­free drinks. Caffeine intoxication The DSM-­519 defines caffeine intoxication as the recent consumption of caffeine, usually in excess of 250mg, accompanied by five or more of the symptoms in Box 12.1. In caffeine intoxication, these symptoms cause significant distress or impairment in social, occupational or other important areas of functioning and are not due to a ­general medical condition or better accounted for by another mental disorder (e.g. an anxiety disorder). Caffeine abuse or dependence as a clinical syndrome has been reported3 and caffeine use disorder and caffeine withdrawal are both DSM-­5 diagnoses. Table 12.3  Interactions with caffeine. Interacting substance Effect Comments CYP1A2 inhibitors: Oestrogens Cimetidine Fluvoxamine (may decrease caffeine clearance by 80%)15 Disulfiram Reduce caffeine clearance Effects of caffeine may be prolonged or increased Adverse effects may be increased May precipitate caffeine toxicity Cigarette smoke* CYP1A2 inducer – increased caffeine metabolism6 Smokers may require higher doses of caffeine to gain desired effects6 Lithium High doses of caffeine may reduce lithium levels Caffeine withdrawal may cause a lithium level rise16 MAOIs May enhance stimulant CNS effects Clozapine Caffeine may increase clozapine plasma concentrations by up to 60%17 Thought to be via competitive inhibition of CYP1A2. Other drugs affected by caffeine-­induced inhibition of the enzyme include olanzapine, imipramine and clomipramine. SSRIs Large doses of caffeine may increase risk of serotonin syndrome18 Benzodiazepines Caffeine may act as an antagonist Caffeine reduces the efficacy of benzodiazepines8 * Vaping has no effect on CYP1A2 function. CNS, central nervous system; MAOIs, monoamine oxidase inhibitors.

05 - Energy drinks

Energy drinks

06 - Effects of caffeine on different disorders

Effects of caffeine on different disorders

904 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 12 Energy drinks So-­called energy drinks contain large amounts of caffeine along with sugar, vitamins and a number of other ingredients such as guarana and taurine. There is some evidence that these drinks can improve attention and short-­term memory.20 Marketing is targeted at adolescents and young adults, some of whom consume large volumes of these drinks and seem to be particularly vulnerable to developing signs and symptoms of caffeine intoxication. Symptoms of anxiety and depression, frank suicidal behaviour and seizures have been associated with use of these products by young people.21–23 When combined with alcohol, aggressive behaviour may result.24 Excessive intake may lead to acute psychosis25,26 or mania.27 Effects of caffeine on different disorders Schizophrenia ■ ■Patients with schizophrenia often consume large amounts of caffeine-­containing drinks1 and they are twice as likely as controls to consume >200mg caffeine/day.6 ■ ■Caffeine-­containing drinks may be used to relieve dry mouth (as an adverse effect of some antipsychotic drugs), for the stimulant effects of caffeine (to relieve dysphoria/ sedation/negative symptoms)6 or simply because coffee/tea drinking structures the day or relieves boredom. ■ ■Schizophrenia may increase sensitivity to drug-­related cues.6 ■ ■Moderate caffeine intake may improve cognitive and negative symptoms in schizophrenia.28,29 ■ ■Large doses of caffeine can worsen psychotic symptoms6,30 (in particular elation and conceptual disorganisation) and result in the prescription of larger doses of antipsychotic drugs. ■ ■The removal of caffeine from the diets of chronically disturbed (challenging behaviour) patients may ultimately lead to decreased levels of hostility, irritability and suspiciousness31 although this may not hold true in less disturbed populations.32 ■ ■Caffeine cessation may be of benefit in clozapine-­resistant schizophrenia.33 Box 12.1  Symptoms of caffeine intoxication ■ ■Restlessness ■ ■Gastrointestinal disturbance ■ ■Nervousness ■ ■Muscle twitching ■ ■Excitement ■ ■Rambling flow of thought and speech ■ ■Insomnia ■ ■Tachycardia or cardiac arrhythmia ■ ■Flushed face ■ ■Periods of inexhaustibility ■ ■Diuresis ■ ■Psychomotor agitation

07 - Summary

Summary

Other substances CHAPTER 12 Mood disorders ■ ■Caffeine may elevate mood through increasing noradrenaline release34 and modest caffeine consumption may protect against depression in those who do not have a pre-­ existing mood disorder.35 ■ ■People with mood disorders are more likely to consume caffeine, particularly when depressed.16,36 ■ ■Depressed patients may be more sensitive to the anxiogenic effects of caffeine.37,38 ■ ■Excessive consumption of caffeine may precipitate mania.38,39 ■ ■Caffeine can increase cortisol secretion (gives a false positive in the dexamethasone-­ suppression test),40 increase seizure length during electroconvulsive therapy41 and increase the clearance of lithium by promoting diuresis.42 Anxiety disorders ■ ■Caffeine increases vigilance, decreases reaction times, increases sleep latency and worsens sleep quality; effects that may be more marked in poor metabolisers. ■ ■May precipitate or worsen generalised anxiety and panic attacks;43 vulnerability to these effects may be genetically determined.11 ■ ■Effects are so marked that caffeine intoxication should always be considered when patients complain of anxiety symptoms or insomnia. ■ ■Symptoms may diminish considerably or even abate completely if caffeine is avoided.44 ■ ■Patients with panic disorder consume much more caffeine than controls45 but the reasons for this are not clear. Greater consumption triggers panic attacks in those with panic disorder but not in other populations.46 Other disorders Weak evidence supports the benefit of caffeine in attention deficit hyperactivity ­disorder (ADHD)47 and that high caffeine consumption may protect against late-­life cognitive decline.48 Summary ■ ■Caffeine is present in high quantities in coffee and some soft drinks, particularly energy drinks. ■ ■The intake of caffeine may worsen psychosis and anxiety. Young people may be particularly vulnerable. ■ ■Caffeine inhibits clozapine metabolism. ■ ■Caffeine intoxication is characterised by psychomotor agitation and rambling speech. ■ ■Caffeine may be associated with toxicity when co-­administered with CYP1A2 inhibitors such as fluvoxamine. ■ ■Caffeine can enhance the reinforcing effects of nicotine and possibly other drugs of misuse.

08 - References

References

906 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 12 References

  1. Rihs M, et al. Caffeine consumption in hospitalized psychiatric patients. Eur Arch Psychiatry Clin Neurosci 1996; 246:83–92.
  2. Clementz GL, et al. Psychotropic effects of caffeine. Am Fam Physician 1988; 37:167–172.
  3. Ogawa N, et al. Clinical importance of caffeine dependence and abuse. Psychiatry Clin Neurosci 2007; 61:263–268.
  4. Desbrow B, et al. An examination of consumer exposure to caffeine from retail coffee outlets. Food Chem Toxicol 2007; 45:1588–1592.
  5. McCusker RR, et al. Caffeine content of decaffeinated coffee. J Anal Toxicol 2006; 30:611–613.
  6. Adolfo AB, et al. Effects of smoking cues on caffeine urges in heavy smokers and caffeine consumers with and without schizophrenia. Schizophr Res 2009; 107:192–197.
  7. Grant JE, et al. Caffeine’s influence on gambling behavior and other types of impulsivity. Addict Behav 2018; 76:156–160.
  8. Sawynok J. Pharmacological rationale for the clinical use of caffeine. Drugs 1995; 49:37–50.
  9. O’Keefe JH, et al. Effects of habitual coffee consumption on cardiometabolic disease, cardiovascular health, and all-­cause mortality. J Am Coll Cardiol 2013; 62:1043–1051.
  10. Pharmaceutical Press. Martindale: The Complete Drug Reference. 2024; www.medicinescomplete.com.
  11. Bergin JE, et al. Common psychiatric disorders and caffeine use, tolerance, and withdrawal: an examination of shared genetic and environmental effects. Twin Res Hum Genet 2012; 15:473–482.
  12. Silverman K, et al. Withdrawal syndrome after the double-­blind cessation of caffeine consumption. N Engl J Med 1992; 327:1109–1114.
  13. Butler MA, et al. Determination of CYP1A2 and NAT2 phenotypes in human populations by analysis of caffeine urinary metabolites. Pharmacogenetics 1992; 2:116–127.
  14. Kaplan GB, et al. Dose-­dependent pharmacokinetics and psychomotor effects of caffeine in humans. J Clin Pharmacol 1997; 37:693–703.
  15. Pharmaceutical Press. Medicines Complete: Stockley’s Drug Interactions. 2024; www.medicinescomplete.com.
  16. Baethge C, et al. Coffee and cigarette use: association with suicidal acts in 352 Sardinian bipolar disorder patients. Bipolar Disord 2009; 11:494–503.
  17. Carrillo JA, et al. Effects of caffeine withdrawal from the diet on the metabolism of clozapine in schizophrenic patients. J Clin Psychopharmacol 1998; 18:311–316.
  18. Ohta R, et al. Serotonin syndrome triggered by overuse of caffeine and complicated with neuroleptic malignant syndrome: a case report. Cureus 2022; 14:e22468.
  19. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th edn (DSM-­5). Arlington, VA: American Psychiatric Association; 2013.
  20. Wesnes KA, et al. An evaluation of the cognitive and mood effects of an energy shot over a 6h period in volunteers: a randomized, double-­ blind, placebo controlled, cross-­over study. Appetite 2013; 67:105–113.
  21. Szpak A, et al. A case of acute suicidality following excessive caffeine intake. J Psychopharmacol 2012; 26:1502–1510.
  22. Trapp GS, et al. Energy drink consumption among young Australian adults: associations with alcohol and illicit drug use. Drug Alcohol Depend 2014; 134:30–37.
  23. Pennington N, et al. Energy drinks: a new health hazard for adolescents. J Sch Nurs 2010; 26:352–359.
  24. Sheehan BE, et al. Caffeinated and non-­caffeinated alcohol use and indirect aggression: the impact of self-­regulation. Addict Behav 2016; 58:53–59.
  25. Görgülü Y, et al. A case of acute psychosis following energy drink consumption. Noro Psikiyatri Arsivi 2014; 51:79–81.
  26. Kelsey D, et  al. A case of psychosis and renal failure associated with excessive energy drink consumption. Case Rep Psychiatry 2019; 2019:3954161.
  27. Rodrigues Cordeiro C, et al. Triggers for acute mood episodes in bipolar disorder: a systematic review. J Psychiatr Res 2023; 161:237–260.
  28. Szoke A, et al. Clinical and pharmacological correlates of caffeine consumption in subjects with schizophrenia – data from the FACE-­SZ cohort. J Psychiatr Res 2023; 161:206–212.
  29. Han Almis B, et al. Is there a relationship between caffeine intake and smoking and positive and negative symptom severity in schizophrenia? Psychiatr Danub 2023; 35:56–61.
  30. Wang HR, et al. Caffeine-­induced psychiatric manifestations: a review. Int Clin Psychopharmacol 2015; 30:179–182.
  31. De Freitas B, et al. Effects of caffeine in chronic psychiatric patients. Am J Psychiatry 1979; 136:1337–1338.
  32. Koczapski A, et al. Effects of caffeine on behavior of schizophrenic inpatients. Schizophr Bull 1989; 15:339–344.
  33. Dratcu L, et al. Clozapine-­resistant psychosis, smoking, and caffeine: managing the neglected effects of substances that our patients consume every day. Am J Ther 2007; 14:314–318.
  34. Achor MB, et al. Diet aids, mania, and affective illness. Am J Psychiatry 1981; 138:392.
  35. Wang L, et al. Coffee and caffeine consumption and depression: a meta-­analysis of observational studies. Aust NZ J Psychiatry 2016; 50:228–242.
  36. Maremmani I, et  al. Are “social drugs” (tobacco, coffee and chocolate) related to the bipolar spectrum? J Affect Disord 2011; 133:227–233.
  37. Lee MA, et al. Anxiogenic effects of caffeine on panic and depressed patients. Am J Psychiatry 1988; 145:632–635.
  38. Rizkallah E, et al. Could the use of energy drinks induce manic or depressive relapse among abstinent substance use disorder patients with comorbid bipolar spectrum disorder? Bipolar Disord 2011; 13:578–580.
  39. Machado-­Vieira R, et al. Mania associated with an energy drink: the possible role of caffeine, taurine, and inositol. Can J Psychiatry 2001; 46:454–455.
  40. Uhde TW, et al. Caffeine-­induced escape from dexamethasone suppression. Arch Gen Psychiatry 1985; 42:737–738.
  41. Cantu TG, et al. Caffeine in electroconvulsive therapy. Ann Pharmacother 1991; 25:1079–1080.

Other substances CHAPTER 12 42. Mester R, et al. Caffeine withdrawal increases lithium blood levels. Biol Psychiatry 1995; 37:348–350. 43. Bruce MS. The anxiogenic effects of caffeine. Postgrad Med J 1990; 66 Suppl 2:S18–S24. 44. Bruce MS, et al. Caffeine abstention in the management of anxiety disorders. Psychol Med 1989; 19:211–214. 45. Santos VA, et al. Panic disorder and chronic caffeine use: a case-­control study. Clin Pract Epidemiol Ment Health 2019; 15:120–125. 46. Klevebrant L, et al. Effects of caffeine on anxiety and panic attacks in patients with panic disorder: a systematic review and meta-­analysis. Gen Hosp Psychiatry 2022; 74:22–31. 47. Ioannidis K, et al. Ostracising caffeine from the pharmacological arsenal for attention-­deficit hyperactivity disorder – was this a correct decision? A literature review. J Psychopharmacol 2014; 28:830–836. 48. Panza F, et al. Coffee, tea, and caffeine consumption and prevention of late-­life cognitive decline and dementia: a systematic review. J Nutr Health Aging 2015; 19:313–328.

09 - Nicotine

Nicotine

10 - Psychotropic effects

Psychotropic effects

11 - Effects of nicotine on different disorders

Effects of nicotine on different disorders

908 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 12 Nicotine Nicotine is consumed by vaping or tobacco smoking and causes peripheral vasoconstriction, tachycardia and increased blood pressure.1 People with schizophrenia who smoke are more likely to develop the metabolic syndrome compared with those who do not smoke.2 Alongside nicotine, cigarettes also contain tar (a complex mixture of organic molecules, many carcinogenic), a cause of cancers of the respiratory tract, chronic ­bronchitis and emphysema.3 Electronic cigarettes and vaping devices contain only nicotine (along with some necessary excipients), which has very limited toxicity and is not thought to be carcinogenic. Vaping is thus preferred for all smokers, albeit with some reservations in regard to quality control of content and the so-­called re-­normalisation of smoking. Vaping is not without risk but this is a complex area beyond the scope of this book. Nicotine is highly addictive and vulnerability to nicotine addiction may be genetically determined.4 People with mental illness are 2–3 times more likely than the general population to develop and maintain a nicotine addiction.5 Chronic smoking contributes to the increased morbidity and mortality from respiratory and cardiovascular disease that is seen in this patient group. Nicotine also has psychotropic effects. Smoking can affect the metabolism (and therefore the efficacy and toxicity) of drugs prescribed to treat psychiatric illness6 (see ‘Smoking and psychotropic drugs’ in Chapter 11). Nicotine use may be a gateway drug to experimenting with other psychoactive substances. Psychotropic effects Nicotine is highly lipid-­soluble and rapidly enters the brain after inhalation. Nicotine receptors are found on dopaminergic cell bodies and stimulation of these receptors leads to dopamine release.5 Nicotine may be used by people with mental health problems as a form of ‘self-­medication’ (e.g. to alleviate the negative symptoms of schizophrenia or antipsychotic-­induced dysphoria or for its anxiolytic effect7). Drugs that increase the release of dopamine reduce craving for nicotine. They may also, of course, worsen ­psychotic illness. Nicotine improves concentration and vigilance,5 probably by enhancing the effects of glutamate, acetylcholine and serotonin.7 Effects of nicotine on different disorders Schizophrenia Before the introduction of vaping, 70–80% of people with schizophrenia regularly smoked cigarettes.8 Now both tobacco use and vaping are more common among people with psychosis.9,10 A 2024 study in the USA11 found that 28% of people with a first episode of psychosis used nicotine in one form or another – roughly double the rate of age-­matched controls. In people with longer-standing psychosis in 2023, tobacco use was seen in just over 40% but use of any nicotine product was reported in around 70–80% (i.e. a prevalence no different from before the availability of vaping devices).12

Other substances CHAPTER 12 This increased tendency to use nicotine predates the onset of psychiatric symptoms13 and smoking might actually be a causal factor in schizophrenia.14 Possible explanations are as follows:15 (i) smoking causes dopamine release, leading to feelings of well-­being and a reduction in negative symptoms;7 (ii) smoking alleviates some of the adverse effects of antipsychotics such as drowsiness and extrapyramidal side effects (EPSEs)5 and cognitive slowing;16,17 (iii) smoking serves as a means of structuring the day (a behavioural filler); (iv) smoking arises as a result of a familial vulnerability;18 or (v) smoking may be used as a means of alleviating the deficit in auditory gaiting that is found in schizophrenia.19 Nicotine may also improve working memory and attentional deficits.20–22 Nicotinic receptor agonists may have beneficial effects on neurocognition,23,24 although none is licensed for this purpose. Note though that cholinergic agonists may exacerbate nicotine dependence.25 Interestingly, the greater the occupancy of striatal D2 receptors by antipsychotic drugs, the more likely the patient is to smoke.26 This may partly explain the clinical observation that smoking cessation may be more achievable when clozapine (a weak dopamine antagonist) is prescribed in place of a conventional antipsychotic. It has been suggested that people with schizophrenia find it particularly difficult to tolerate nicotine withdrawal symptoms6 (although some certainly can stop27). Switching to nicotine replacement therapy or vaping may thus be the preferred option.28,29 A switch from tobacco smoking to vaping has been shown to be well ­tolerated even in severe mental illness.30 Depression and anxiety Moderate consumption of nicotine is associated with pleasure and a decrease in anxiety and feelings of anger.31 The mechanism of this anxiolytic effect is not understood. People who suffer from anxiety and/or depression are more likely to smoke32 and find it more difficult to stop.31,33 Nicotine itself might have antidepressant activity.34 Nicotine withdrawal can precipitate or exacerbate depression in those with a history of the illness,31 but cigarette smoking may directly increase the risk of depression.35 A 2020 study suggested nicotine addiction and depression are independently linked.36 Some studies suggest that stopping smoking ultimately improves depression and anxiety.37,38 A 2020 Cochrane review39 suggests smoking cessation is achievable in depressed ­smokers, but a later twin study found that depression made smoking cessation much less likely.40 Patients with depression are at increased risk of cardiovascular disease. By directly causing tachycardia and hypertension,1 nicotine may, in theory, exacerbate this problem. More importantly, smoking tobacco is a well-­known independent risk factor for cardiovascular disease, probably because it hastens atherosclerosis. Vaping, while not carcinogenic, increases risk of cardiovascular disease.41 Attention deficit hyperactivity disorder (ADHD) People with ADHD are relatively more likely to use nicotine products.42 Tobacco smoke contains monoamine oxidase inhibitors which may benefit ADHD symptoms.43 There is ample evidence of complex pharmacodynamic interactions between nicotine and stimulant drugs.44

12 - Drug interactions

Drug interactions

13 - Smoking cessation and withdrawal symptoms

Smoking cessation and withdrawal symptoms

14 - References

References

910 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 12 Movement disorders and Parkinson’s disease By increasing dopaminergic neurotransmission, nicotine is thought to provide a protective effect against both drug-­induced EPSEs and idiopathic Parkinson’s disease. Smokers are less likely to suffer from antipsychotic-­induced movement disorders than non-­smokers5 and use anticholinergic drugs less often.6 Parkinson’s disease occurs less frequently in smokers than in non-­smokers and the onset of clinical symptoms is delayed.5,45 This may reflect the inverse association between Parkinson’s disease and sensation-­seeking behavioural traits, rather than a direct effect of nicotine.46 The protective effect may not be related to nicotine at all but rather to other compounds in tobacco smoke.47 Drug interactions Polycyclic hydrocarbons in tobacco smoke are known to stimulate the hepatic microsomal enzyme system, particularly CYP1A2,7 the enzyme responsible for the metabolism of many psychotropic drugs. Smoking can lower the blood levels of some drugs by more than 50%.7 This can both affect efficacy and influence adverse effects and needs to be taken into account when making clinical decisions. The drugs most likely to be affected are clozapine,48 fluphenazine, haloperidol, chlorpromazine, olanzapine, many tricyclic antidepressants, mirtazapine, fluvoxamine and propranolol. Vaping has no effect on hepatic enzyme function. See ‘Smoking and psychotropic drugs’ in Chapter 11. Smoking cessation and withdrawal symptoms Withdrawal symptoms occur within 6–12 hours of stopping smoking and include intense craving, depressed mood, insomnia, anxiety, restlessness, irritability, difficulty in concentrating and increased appetite. Nicotine withdrawal can be misdiagnosed as depression, anxiety, sleep disorders and mania.49 Withdrawal can also exacerbate the symptoms of schizophrenia.6 See also ‘Nicotine and smoking cessation’ in Chapter 4. References

  1. Benowitz NL, et al. Cardiovascular effects of nasal and transdermal nicotine and cigarette smoking. Hypertension 2002; 39:1107–1112.
  2. Yevtushenko OO, et al. Influence of 5-­HT2C receptor and leptin gene polymorphisms, smoking and drug treatment on metabolic disturbances in patients with schizophrenia. Br J Psychiatry 2008; 192:424–428.
  3. Anderson JE, et al. Treating tobacco use and dependence: an evidence-­based clinical practice guideline for tobacco cessation. Chest 2002; 121:932–941.
  4. Berrettini W. Nicotine addiction. Am J Psychiatry 2008; 165:1089–1092.
  5. Goff DC, et al. Cigarette smoking in schizophrenia: relationship to psychopathology and medication side effects. Am J Psychiatry 1992; 149:1189–1194.
  6. Ziedonis DM, et al. Schizophrenia and nicotine use: report of a pilot smoking cessation program and review of neurobiological and clinical issues. Schizophr Bull 1997; 23:247–254.
  7. Lyon ER. A review of the effects of nicotine on schizophrenia and antipsychotic medications. Psychiatr Serv 1999; 50:1346–1350.
  8. Winterer G. Why do patients with schizophrenia smoke? Curr OpinPsychiatry 2010; 23:112–119.
  9. Sharma R, et al. Motivations and limitations associated with vaping among people with mental illness: a qualitative analysis of Reddit ­discussions. Int J Environ Res Public Health 2016; 14:7.
  10. Bianco CL. Rates of electronic cigarette use among adults with a chronic mental illness. Addict Behav 2019; 89:1–4.
  11. Bennett ME, et al. Tobacco smoking and nicotine vaping in persons with first episode psychosis. Schizophr Res 2024; 267:141–149.
  12. Han B, et al. Tobacco use, nicotine dependence, and cessation methods in US adults with psychosis. JAMA Network Open 2023; 6:e234995.
  13. Weiser M, et al. Higher rates of cigarette smoking in male adolescents before the onset of schizophrenia: a historical-­prospective cohort study. Am J Psychiatry 2004; 161:1219–1223.
  14. Hunter A, et al. The effects of tobacco smoking, and prenatal tobacco smoke exposure, on risk of schizophrenia: a systematic review and meta-­analysis. Nicotine Tob Res 2020; 22:3–10.

Other substances CHAPTER 12 15. Caponnetto P, et al. Tobacco smoking, related harm and motivation to quit smoking in people with schizophrenia spectrum disorders. Health Psychol Res 2020; 8:9042. 16. Harris JG, et al. Effects of nicotine on cognitive deficits in schizophrenia. Neuropsychopharmacology 2004; 29:1378–1385. 17. Gupta T, et al. Nicotine usage is associated with elevated processing speed, spatial working memory, and visual learning performance in youth at ultra high-­risk for psychosis. Psychiatry Res 2014; 220:687–690. 18. Ferchiou A, et al. Exploring the relationships between tobacco smoking and schizophrenia in first-­degree relatives. Psychiatry Res 2012; 200:674–678. 19. McEvoy JP, et al. Smoking and therapeutic response to clozapine in patients with schizophrenia. Biol Psychiatry 1999; 46:125–129. 20. Jacobsen LK, et al. Nicotine effects on brain function and functional connectivity in schizophrenia. Biol Psychiatry 2004; 55:850–858. 21. Sacco KA, et al. Effects of cigarette smoking on spatial working memory and attentional deficits in schizophrenia: involvement of nicotinic receptor mechanisms. Arch Gen Psychiatry 2005; 62:649–659. 22. Smith RC, et al. Effects of nicotine nasal spray on cognitive function in schizophrenia. Neuropsychopharmacology 2006; 31:637–643. 23. Olincy A, et al. Proof-­of-­concept trial of an alpha7 nicotinic agonist in schizophrenia. Arch Gen Psychiatry 2006; 63:630–638. 24. Lieberman JA, et al. Cholinergic agonists as novel treatments for schizophrenia: the promise of rational drug development for psychiatry. Am J Psychiatry 2008; 165:931–936. 25. Kelly DL, et al. Lack of beneficial galantamine effect for smoking behavior: a double-­blind randomized trial in people with schizophrenia. Schizophr Res 2008; 103:161–168. 26. De Haan L, et al. Occupancy of dopamine D2 receptors by antipsychotic drugs is related to nicotine addiction in young patients with schizophrenia. Psychopharmacology (Berl) 2006; 183:500–505. 27. Gilbody S, et al. Smoking cessation for people with severe mental illness (SCIMITAR+): a pragmatic randomised controlled trial. Lancet Psychiatry 2019; 6:379–390. 28. Caponnetto P, et al. Impact of an electronic cigarette on smoking reduction and cessation in schizophrenic smokers: a prospective 12-­month pilot study. Int J Environ Res Public Health 2013; 10:446–461. 29. Kozak K, et  al. Pharmacotherapy for smoking cessation in schizophrenia: a systematic review. Expert Opin Pharmacother 2020; 21:581–590. 30. Hickling LM, et al. A pre-­post pilot study of electronic cigarettes to reduce smoking in people with severe mental illness. Psychol Med 2019; 49:1033–1040. 31. Glassman AH. Cigarette smoking: implications for psychiatric illness. Am J Psychiatry 1993; 150:546–553. 32. Cai J, et al. E-­cigarette use or dual use of E-­cigarette and combustible cigarette and mental health and cognitive impairment: findings from the National Health Interview Survey, 2020–2021. J Affect Disord 2024; 351:878–887. 33. Wilhelm K, et al. Clinical aspects of nicotine dependence and depression. Med Today 2004; 5:40–47. 34. Gandelman JA, et al. Transdermal nicotine for the treatment of mood and cognitive symptoms in nonsmokers with late-­life depression. J Clin Psychiatry 2018; 79:18m12137. 35. Boden JM, et  al. Cigarette smoking and depression: tests of causal linkages using a longitudinal birth cohort. Br J Psychiatry 2010; 196:440–446. 36. Bainter T, et  al. A key indicator of nicotine dependence is associated with greater depression symptoms, after accounting for smoking ­behavior. PLoS One 2020; 15:e0233656. 37. Taylor G, et al. Change in mental health after smoking cessation: systematic review and meta-­analysis. BMJ 2014; 348:g1151. 38. Cather C, et  al. Improved depressive symptoms in adults with schizophrenia during a smoking cessation attempt with varenicline and ­behavioral therapy. J Dual Diagn 2017; 13:168–178. 39. Van der Meer RM, et al. Smoking cessation interventions for smokers with current or past depression. Cochrane Database Syst Rev 2013; 8:CD006102. 40. Ranjit A, et  al. Depressive symptoms predict smoking cessation in a 20-­year longitudinal study of adult twins. Addict Behav 2020; 108:106427. 41. Zong H, et al. Electronic cigarettes and cardiovascular disease: epidemiological and biological links. Pflugers Arch 2024; 476:875–888. 42. Xu G, et al. Association of attention-­deficit/hyperactivity disorder with E-­cigarette use. Am J Prev Med 2021; 60:488–496. 43. Taylor MR, et al. Tobacco and ADHD: a role of MAO-­inhibition in nicotine dependence and alleviation of ADHD symptoms. Front Neurosci 2022; 16:845646. 44. McNealy KR, et al. The co-­use of nicotine and prescription psychostimulants: a review of their behavioral and neuropharmacological interactions. Drug Alcohol Depend 2023; 248:109906. 45. Scott WK, et al. Family-­based case-­control study of cigarette smoking and Parkinson disease. Neurology 2005; 64:442–447. 46. Evans AH, et al. Relationship between impulsive sensation seeking traits, smoking, alcohol and caffeine intake, and Parkinson’s disease. J Neurol Neurosurg Psychiatry 2006; 77:317–321. 47. Rose KN, et al. Clearing the smoke: what protects smokers from Parkinson’s disease? Mov Disord 2024; 39:267–272. 48. Derenne JL, et al. Clozapine toxicity associated with smoking cessation: case report. Am J Ther 2005; 12:469–471. 49. Conti AA, et al. Severity of negative mood and anxiety symptoms occurring during acute abstinence from tobacco: a systematic review and meta-­analysis. Neurosci Biobehav Rev 2020; 115:48–63.